Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy.

Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy.
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丰富的环境通过促进自噬促进中风后神经功能的恢复

DOI:
10.4103/1673-5374.297084
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发表时间:
2021-05
影响因子:
6.1
通讯作者:
He HY
He HY
中科院分区:
医学2区
文献类型:
--
作者:
Deng YH;Dong LL;Zhang YJ;Zhao XM;He HY

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自噬对于维持细胞内稳态至关重要,并且可以在缺血性卒中后被激活。它还参与神经损伤和修复。本研究的目的是探讨丰富的环境是否通过影响自噬而具有神经保护作用。通过阻塞大脑中动脉然后再灌注制备短暂性缺血性中风的Sprague-Dawley大鼠模型。手术后一周,将这些大鼠在标准环境或丰富环境中连续饲养4周。丰富的环境增加Beclin-1的表达和LC 3-II/LC 3-I的比例在自噬/溶酶体途径中的大脑中动脉闭塞大鼠的半影区。丰富的环境诱导的自噬活性的升高主要在神经元中观察到。丰富的环境处理还促进了自噬体与溶酶体的融合,增强了溶酶体相关膜蛋白1、组织蛋白酶B和组织蛋白酶D的溶酶体活性,并降低了泛素和p62的表达。丰富环境治疗4周后,大脑中动脉闭塞/再灌注引起的神经功能缺损和神经元死亡明显减轻,梗死体积明显缩小。这些发现表明,神经元自噬可能是丰富的环境促进缺血性卒中恢复的神经保护机制。本研究于2019年3月1日获得中国昆明理工大学动物伦理委员会批准(批准号:5301002013855)。
Autophagy is crucial for maintaining cellular homeostasis, and can be activated after ischemic stroke. It also participates in nerve injury and repair. The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy. A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion. One week after surgery, these rats were raised in either a standard environment or an enriched environment for 4 successive weeks. The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats. Enriched environment-induced elevations in autophagic activity were mainly observed in neurons. Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes, enhanced the lysosomal activities of lysosomal-associated membrane protein 1, cathepsin B, and cathepsin D, and reduced the expression of ubiquitin and p62. After 4 weeks of enriched environment treatment, neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated, and infarct volume was significantly reduced. These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke. This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology, China (approval No. 5301002013855) on March 1, 2019.
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期刊: Redox biology
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影响因子: 21.3
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